A generous body of evidence suggests that low renin essential hypertension is a mineralocorticoid syndrome, and the absence of hypokalemic alkalosis suggests that the etiologic steroid(s) causes dissociation of hypertensenogenic and kaliuretic properties. Recently it has been described that these patients have an increased fraction of urinary bioassayable mineralocorticoid activity not explained by excretion of the known mineralocorticoids. This fraction is partially attributed to the excretion of increased amounts of 16 Beta-hydroxy dehydroepiandrosterone, a previously undescribed C-19 mineralocorticoid with a potency 1/40th that of aldosterone. The etiology of low renin hypertension is suggested to be secondary to increased production of this steroid, or perhaps a family of steroids dependent on the 16 Beta-hydroxylase enzyme. Two further members of this family, 16-Oxo-androstenediol and 16-keto testosterone have been described to have mineralocorticoid activity. Inability to attribute all of the unexplained mineralocorticoid activity to 16-Beta-OH-DHEA raises the distinct possibility that other, possibly more active, members of this family may exist. We have synthesized these three steroids and have confirmed a weak mineralocorticoid potency by the rat bioassay. Further evaluation of bioassayable mineralocorticoid activity contributed by the known mineralocorticoids and the recently described C-19 mineralocorticoids is needed. At the present time we have partially developed radioimmunoassays for 16 Beta-OH-DHEA and 16-Oxo-A-diol. We propose to use these assays and assays which will be developed for any other active C-19 mineralocorticoids to quantitate the plasma and urinary mineralocorticoid effects contributed by the C-19 mineralocorticoids and to study their production rates, regulatory mechanisms, and metabolism. In addition we will further explore their effects on renal mineralocorticoid receptors and will study their hypertensenogenic properties in the rat. These studies should elucidate considerably the role of the C-19 mineralocorticoids in low renin hypertension.